This is a renewal application for our major grant support. Our basic aim is to understand the mechanism of platelet function which leads to in vivo thrombus formation. Therefore models of platelet function which include platelet adhesion to glass and collagen and thrombus formation on damaged blood vessels will be developed. The role of platelet energy utilization and the role of the release reaction in these models will be studied. The effects of different flow parameters on platelet energy utilization and thrombus formation will also be evaluated. Ultimately we plan to study the effects of drugs which inhibit in vitro platelet aggregation to determine if they similarly inhibit platelet function in these models. Specifically we plan to determine if these drugs prevent thrombus formation and if they do, whether they act by affecting platelet energy production or energy utilization. Finally we hope to study platelets from patients with thrombotic disorders to determine if their behavior in these models is different from normal.